There is a growing body of information that viruses play a vital role in a broad range of diseases, some of which represent the most serious of man's ills. Arthritis, juvenile arthritis, diabetes, Hodgkin's disease and various immunological diseases and degenerative diseases of the central nervous system have been linked to viruses as the causative agents.
At present, the control of virus infections is primarily achieved by means of immunization vaccines. For example, poliomyelitis, smallpox, measles and influenza are well recognized diseases in which viral vaccines have proven effective. In general, however, viral vaccines have had only a moderate success in animal prophylaxis. Each vaccine acts primarily against a specific virus and is not heterophilic in the protection it offers. Hence, vaccines do not provide a practical solution against the wide array of infectious viruses, even when limited as for example, solely to respiratory viruses.
One approach to the control of virus-related diseases and, particularly to the spread of such virus diseases, has been to search for medicinal agents or chemotherapeutic agents which are capable of inhibiting the growth of viruses, thereby preventing the spread of disease as well as preventing further damage to cells and tissues of the animal host which have not as yet been infected. Heretofore, only a limited number of virus infections such as smallpox, Asian influenza and herpes keratitis have been susceptible to prevention by chemical antiviral agents. Sulfonamides and antibiotics which have revolutionized the treatment of bacterial infections have substantially no effect upon virus infections. Certain infections caused by large viruses, such as lymphogranuloma venereum, psittacosis and trachoma have been successfully treated using antibiotics and sulfa drugs. However, the majority of infections have not been responsive to attack by chemotherapeutic agents. Thus, it can be seen that there is a need for new chemotherapeutic agents which are effective against a broad range of virus diseases, and which at the same time, are non-toxic to the host.
As a result of a long series of investigations, applicants have discovered a novel class of bis-basic esters of phenanthrene and 9-oxa and 9-aza phenanthrene which are particularly useful antiviral agents. These compounds are effective against a wide spectrum of virus infections and are useful in treating such infections either prophylactically or therapeutically.
U.S. Pat. Nos. 3,531,489; 3,647,860 and 3,662,062 represent the closest art known to applicants and disclose esters and thioesters of fluorene, fluorenol, fluorenone and fluoranthene which are useful as antiviral agents. Certain of the compounds disclosed in U.S. Pat. No. 3,662,062 serve as starting materials for the preparation of the compounds of the present invention. The bis-basic esters described and claimed herein, however, are derived from totally different and non-related 6,6,6 membered aromatic ring systems which differ substantially from either the fluorene or fluoranthene nucleus. To applicants' knowledge the compounds described and claimed herein are novel compounds which have not previously been described nor reported in the literature. Furthermore, applicants are unaware of any previously reported bis basic derivatives of phenanthrene or derivatives of 9-oxa and 9-aza phenanthrene whatsoever which possess antiviral activity. The instant compounds possess a wide spectrum of antiviral activity in varying degrees which could not, therefore, have been predicted from a knowledge of the present state of the art.